Epub: Jelcic et al. T Cell Epitope Mapping of JC Polyoma Virus-Encoded Proteome Reveals Reduced T Cell Responses in HLA-DRB1*04:01+ Donors. J Virol. 2013 Jan.
Background: JC polyoma virus (JCV) infection is highly prevalent and usually kept in a persistent state without clinical signs and symptoms. Only during immunocompromise and especially impaired CD4(+) T cell function in the brain, as seen in AIDS patients or natalizumab-treated MSers, JCV may cause progressive multifocal leukoencephalopathy (PML), an often life-threatening brain disease. Since CD4(+) T cells are likely play an important role in controlling JCV infection, we here describe the T cell response against JCV in a group of predominantly HLA-DR-heterozygotic healthy donors (HD) by using a series of overlapping 15-mer peptides spanning all JCV-encoded open reading frames.
JC polyoma virus = JC Virus or the John Cunningham virus; please note that JC does not refer to Jesus Christ.
HLA-DR are the molecules that antigen-presenting cells use to post protein signals on their surfaces so that immune cells can see them. If the messages in these HLA molecules are foreign then the T-cells become activated and cause inflammation.
The HLA molecules display small proteins or peptides in their groove for the T cells to sample. The following cartoon shows how the HLA with its peptide stimulates the T-cell via its receptor
Results: These investigators identified immunodominant epitopes and compared T cell responses with anti-JCV VP1 antibody production and with the presence of urinary viral shedding. They observed positive JCV-specific T cell responses in 28.6-77.6%, humoral or antibody immune response in 42.6-89.4% and urinary viral shedding in 36.4-45.5% of HD depending on the threshold. Four immunodominant peptides were mapped, and at least one immunogenic peptide per HLA-DRB1 allele was detected in DRB1*01(+), DRB1*07(+), DRB1*11(+), DRB1*13(+), DRB1*15(+), and DRB1*03(+) individuals.
Conclusions: These investigators show for the first time, that JCV-specific T cell responses may be directed not only against JCV VP1 and Large T antigen, but also against all other JCV-encoded proteins. Heterozygotic DRB1*04:01(+) individuals showed very low T cell responses to JCV together with normal anti-VP1 antibody levels and no urinary viral shedding, indicating a dominant-negative effect of this allele on global JCV-directed T cell responses. Our data are potentially relevant for the development of vaccines against JCV.
“This type of research is important and may lead to natalizumab being safer.”